Number of aberrant crypt foci in the rectum is a useful surrogate marker of colorectal adenoma recurrence

Aim: Endoscopic screening and removal of colorectal adenomas can reduce the incidence of colorectal cancer. However, given the possibility of adenoma recurrence, surveillance colonoscopy is currently recommended after the initial screening and removal of colorectal adenomas. Aberrant crypt foci (ACF) have been shown to serve as a reliable surrogate marker of colorectal carcinogenesis. In this study, the relationship between the number of ACF at the initial endoscopic polypectomy and the likelihood of colorectal adenoma recurrence after polypectomy were investigated. Methods: High‐magnification chromoscopic colonoscopy was performed in 82 subjects who underwent endoscopic polypectomy to identify ACF in the lower rectum. Surveillance colonoscopy was then performed 3 years after the baseline polypectomy at Yokohama City University Hospital. Results: The number of ACF was greater in patients who showed adenoma recurrence (7.88 ± 6.35) than in those who did not (2.19 ± 2.95) (P < 0.001). Receiver–operating curve analysis showed that the number of ACF was a highly specific predictor of the risk of adenoma recurrence. Conclusions: This is the first study conducted to investigate the relationship between the number of ACF after endoscopic polypectomy and the likelihood of recurrence of colorectal adenomas. These results suggest that the number of ACF is a useful predictor of the likelihood of colorectal adenoma recurrence.     

Skeletal muscle growth defect in human growth hormone transgenic rat is accompanied by phenotypic changes in progenitor cells

Growth hormone (GH) is known to have a pivotal role in the maintenance of skeletal muscle mass. Sarcopenia, the loss of skeletal muscle mass, is a common phenomenon in aging, and it is widely accepted that sarcopenia is largely attributed to age-related decline in GH secretion. In the present study, we tested if human growth hormone transgenic rats (GH-TG rats) whose plasma GH levels are maintained relatively low could be an appropriate model for sarcopenia. Analyses of GH-TG rats revealed that they exhibit skeletal muscle growth defect as well as atrophy of myofibers. The number of myofibers in tibialis anterior muscle was comparable to that of WT rats, while the proportion of type I slow myofibers in tibialis anterior muscle was increased in GH-TG rats after 5 months. Neither increased expression of ubiquitin ligases, MuRF1 and MAFbx, nor indication of apoptotic cell death was observed. Notably, myogenic differentiation potential of skeletal muscle progenitor cells in GH-TG rats was lower than WT rats, and this was accompanied by increased adipogenic potential. These results indicate that GH-TG rats could be a useful model to elucidate the mechanism of sarcopenia induced by reduced GH action and raised the possibility that decreased GH action may cause an alteration of differentiation potential of skeletal muscle progenitor cells.     

Differences in atherosclerotic profiles between patients with thoracic and abdominal aortic aneurysms

Differences in atherosclerotic profiles between patients with thoracic aortic aneurysm (TAA) and patients with abdominal aortic aneurysm (AAA) have not been studied. We retrospectively studied the clinical records of 343 consecutive patients (132 TAA and 211 AAA) who were admitted to our hospital for elective repair of aortic aneurysms between July 2001 and December 2004. Clinical variables were compared between patients with TAA and those with AAA by using a univariate analysis, and those achieving statistical significance were subsequently assessed in a multivariate analysis. The incidence of coronary artery disease (CAD) (53% vs 23%, p <0.0001), 3-vessel coronary disease (41% vs 10%, p <0.0001), male gender (86% vs 74%, p <0.01), smoker (88% vs 76%, p <0.01), chronic obstructive pulmonary disease (COPD) (30% vs 15%, p <0.01), and diabetes mellitus (39% vs 23%, p <0.01) were significantly higher in patients with AAA than in those with TAA. In contrast, the incidence of hypertension (91% vs 81%, p <0.05), saccular-type aneurysm (61% vs 7%, p <0.0001), and body mass index (24.1 +/- 3.1 vs 23.2 +/- 3.5, p <0.05) were significantly higher in patients with TAA than in those with AAA. Multivariate stepwise logistic analysis revealed that CAD (odds ratio [OR] 3.65; 95% confidence interval [CI] 2.12 to 6.42; p <0.0001), COPD (OR 2.05; 95% CI 1.11 to 3.89; p <0.05), and diabetes mellitus (OR 1.85; 95% CI 1.06 to 3.27; p <0.05) were associated with AAA, and that body mass index (OR 9.39; 95% CI 2.0 to 46.8; p <0.01), hypertension (OR 3.09; 95% CI 1.48 to 6.87; p <0.01), and cerebral infarction (OR 2.83; 95% CI 1.25 to 6.50; p <0.05) were associated with TAA. In conclusion, atherosclerotic profiles are significantly different between patients with TAA and patients with AAA. This result suggests the possibility that mechanisms underlying the development of aortic aneurysms may differ between TAA and AAA, and, from the perspective of prevention, provides further stimulus for the modification of key risk factors for atherosclerosis.     

A novel videoendoscopy system by using autofluorescence and reflectance imaging for diagnosis of esophagogastric cancers

BACKGROUND: Image quality of the prior autofluorescence (AF) imaging systems, including the fiber-optic endoscope, was not feasible for general clinical use. The use of AF image alone resulted in low specificity. The objective of the study was to evaluate the resolution and the sensitivity of the novel videoendoscopy system by using AF and reflectance imaging (AFI) in the diagnosis of early esophagogastric cancers. METHODS: This was a case series study. The setting was a pretreatment examination at a cancer center. Five patients with superficial esophageal cancers (SEC) and 21 patients with 22 early gastric cancers (EGC) were included in the study. The extent of the tumors was diagnosed by white light (WL), AF and chromoendoscopic observations. The main outcome measurement was the diagnostic accuracy of each observation in relation to the histologic mapping as a criterion standard. RESULTS: Two of 5 SECs (40%) were correctly diagnosed in the WL image and all (100%) in the AF image as purple or magenta color in a green background. EGCs in atrophic mucosa were observed as purple or magenta areas in a green background, while diffuse-type EGCs in fundic mucosa were observed as green areas in a purple background. Of the 22 EGCs, diagnostic accuracy of WL, AF, and chromoendoscopic observations were 36%: 95% CI [16%, 56%], 68%: 95% CI [49%, 88%], and 91%: 95% CI [79%, 100%], respectively. AFI could reveal flat or isochromatic extensions that were not detected in the WL images. The limitations of the study were ulcerations or inflammation that caused overdiagnosis in the AF observation. CONCLUSIONS: The resolution of the AFI at present is limited, but the image quality was acceptable. The current system of AFI does not equal to chromoendoscopy in sensitivity but has an advantage over standard WL videoendoscopy.     

Tranilast inhibits the proliferation of uterine leiomyoma cells in vitro through G1 arrest associated with the induction of p21(waf1) and p53

Uterine leiomyoma is a mesenchymal tumor composed of smooth muscle cells with fibrous tissues and many mast cells. Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells. In this study, we examined the effects of tranilast on cultured human leiomyoma cells in vitro to evaluate whether this agent has the potential to inhibit the growth of uterine leiomyomas. Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis. In association with the inhibitory effect, tranilast induced the cyclin-dependent kinase (CDK) inhibitor p21(waf1) and tumor suppressor gene p53 and decreased CDK2 activity. These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21(waf1) and p53. Tranilast was concluded to be a potent agent to inhibit proliferative activity of uterine leiomyoma cells.     

Free-to-total leptin ratio in maternal plasma is constant throughout human pregnancy

To clarify the mechanism of leptin resistance during pregnancy, we measured plasma leptin concentrations, free to total leptin ratio (percent free leptin) and soluble leptin receptor concentrations in pregnant women, and compared the results with those in non-pregnant women. We collected plasma samples from 23 non-pregnant and 31 pregnant women in the third trimester. Plasma samples from 5 pregnant women were collected longitudinally in each trimester. Plasma leptin concentrations in pregnant women in the second trimester (17.4 +/- 3.2 ng/ml) were higher than those in the first trimester of pregnancy (11.0 +/- 2.8 ng/ml, n = 5), as previously reported. However, percent free leptin did not change significantly throughout pregnancy. Percent free leptin correlated with total leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P < 0.0001), but not in women in the third trimester of pregnancy (r = 0.006). Constant percent free leptin during pregnancy despite increased leptin concentrations indicates increased leptin binding capacity in pregnant women, that might partly contribute to the establishment of leptin resistance. On the other hand, soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women (r = -0.470, P < 0.01 and r = -0.493, P < 0.01, respectively) but not in non-pregnant women. These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women.     

Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 ¹¹C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) ¹¹C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on ¹¹C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 ¹¹C-choline-PET/CT scans, respectively. In 27 cases (48.2%), ¹¹C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ± 3.21, 5.95 ± 3.96, 6.73 ± 5.04, and 7.91 ± 3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.     

Acute depressor effect of alcohol in patients with essential hypertension.

To investigate the time course of the effects of alcohol on blood pressure, we studied the response of ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the alcohol intake period than in the control period (125 +/- 3/74 +/- 2 versus 132 +/- 4/78 +/- 2 mm Hg, p less than 0.05), and the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular resistance as determined by echocardiography. Plasma catecholamine levels and renin activity rose significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day. Blood glucose and serum insulin levels were comparable between the two periods. Three patients with marked alcohol-induced flush had greater hypotensive and tachycardiac responses than those who did not show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for assessing blood pressure in habitual drinkers.     

Increased Levels of Human Hepatocyte Growth Factor in Serum and Peritoneal Fluid After Partial Hepatectomy

Objective/Method : It has been reported that inflammatory cytokines up-regulate human hepatocyte growth factor synthesis in vitro. lo demonstrate the relation of this growth factor to interleukin-6 and tumor necrosis factor a, the changes in the levels of these cytokines were measured in serum and peritoneal fluid in 22 patients after partial hepatectomy. Results : Serum and fluids levels of cytokines showed a maximum within 3 days after surgery. Cytokines concentrations were much higher in fluid than in serum (p < 0.05). The maximum serum levels of human hepatocyte growth factor were significantly correlated with those of interleukin-6, intraoperative blood loss, and operating time (p < 0.05) but not with resected liver weights. In fluid level, the growth factor was also correlated with interleukin-6 (p < 0.05) but not with tumor necrosis factor α. Conclusions : These results suggest that human hepatocyte growth factor might be locally produced in the injured tissue associated with interleukin-6 and independently of resected liver weights.